ES2267737T3 - Derivados de imidazopiridinas alquiladas. - Google Patents

Derivados de imidazopiridinas alquiladas. Download PDF

Info

Publication number: ES2267737T3
Authority: ES; Spain
Prior art keywords: alkyl; alkoxy; hydrogen; radical; substituents
Prior art date: 2000-03-29
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES01917121T

Other languages

English (en)

Spanish (es)

Inventor

Stefan Postius

Wolfgang Kromer

Jorg Senn-Bilfinger

Wilm Buhr

Wolfgang-Alexander Simon

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Takeda GmbH

Original Assignee

Altana Pharma AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-03-29

Filing date

2001-03-28

Publication date

2007-03-16

2001-03-28 Application filed by Altana Pharma AG filed Critical Altana Pharma AG

2007-03-16 Application granted granted Critical

2007-03-16 Publication of ES2267737T3 publication Critical patent/ES2267737T3/es

2021-03-28 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

125000003545 alkoxy group Chemical group 0.000 claims abstract description 171
239000001257 hydrogen Substances 0.000 claims abstract description 150
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 150
125000000217 alkyl group Chemical group 0.000 claims abstract description 138
150000001875 compounds Chemical class 0.000 claims abstract description 136
-1 2-alkynyl -4C Chemical group 0.000 claims abstract description 87
125000001424 substituent group Chemical group 0.000 claims abstract description 70
125000003342 alkenyl group Chemical group 0.000 claims abstract description 59
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 58
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 56
229910052736 halogen Inorganic materials 0.000 claims abstract description 41
150000002367 halogens Chemical class 0.000 claims abstract description 41
229910052760 oxygen Inorganic materials 0.000 claims abstract description 35
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 34
239000001301 oxygen Substances 0.000 claims abstract description 34
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 27
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 22
125000001118 alkylidene group Chemical group 0.000 claims abstract description 16
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 16
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
125000002947 alkylene group Chemical group 0.000 claims abstract description 11
125000000304 alkynyl group Chemical group 0.000 claims abstract description 6
150000002431 hydrogen Chemical group 0.000 claims description 103
150000003254 radicals Chemical class 0.000 claims description 50
150000003839 salts Chemical class 0.000 claims description 32
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
239000000460 chlorine Chemical group 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 14
229920001577 copolymer Chemical class 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
229910052801 chlorine Inorganic materials 0.000 claims description 11
239000011737 fluorine Chemical group 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
230000002496 gastric effect Effects 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 7
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 6
229940079593 drug Drugs 0.000 claims description 6
125000003884 phenylalkyl group Chemical group 0.000 claims description 6
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
230000002265 prevention Effects 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 9
229910006069 SO3H Inorganic materials 0.000 claims 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
239000000203 mixture Substances 0.000 description 40
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
239000002253 acid Substances 0.000 description 22
238000002844 melting Methods 0.000 description 21
230000008018 melting Effects 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
238000000034 method Methods 0.000 description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
239000000243 solution Substances 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
239000003480 eluent Substances 0.000 description 13
239000002904 solvent Substances 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
238000002360 preparation method Methods 0.000 description 11
239000000047 product Substances 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
239000012141 concentrate Substances 0.000 description 8
239000013078 crystal Substances 0.000 description 8
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 8
150000007513 acids Chemical class 0.000 description 7
229910052763 palladium Inorganic materials 0.000 description 7
229940002612 prodrug Drugs 0.000 description 7
239000000651 prodrug Substances 0.000 description 7
238000004440 column chromatography Methods 0.000 description 6
238000001816 cooling Methods 0.000 description 6
238000006264 debenzylation reaction Methods 0.000 description 6
239000011343 solid material Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 5
239000012043 crude product Substances 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
239000000463 material Substances 0.000 description 5
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000012047 saturated solution Substances 0.000 description 5
230000028327 secretion Effects 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
210000002784 stomach Anatomy 0.000 description 5
IYVLJJWENFDKKI-LMMKCTJWSA-N (7r,8s,9r)-2,3,8-trimethyl-9-phenyl-9,10-dihydro-7h-imidazo[1,2-h][1,7]naphthyridine-7,8-diol Chemical compound C1([C@H]2NC=3C4=NC(=C(N4C=CC=3[C@@H](O)[C@]2(O)C)C)C)=CC=CC=C1 IYVLJJWENFDKKI-LMMKCTJWSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
241000282414 Homo sapiens Species 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
241000700159 Rattus Species 0.000 description 4
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000006266 etherification reaction Methods 0.000 description 4
VQTUBCCKSQIDNK-UHFFFAOYSA-N iso-butene Natural products CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
238000011321 prophylaxis Methods 0.000 description 4
239000011734 sodium Substances 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
239000007858 starting material Substances 0.000 description 4
KTOQRRDVVIDEAA-UHFFFAOYSA-N 2-methylpropane Chemical compound [CH2]C(C)C KTOQRRDVVIDEAA-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
229940125898 compound 5 Drugs 0.000 description 3
XFZLCTUONFKKGV-UHFFFAOYSA-N ethyl 2,3-dimethyl-8-phenylmethoxyimidazo[1,2-a]pyridine-6-carboxylate Chemical compound C12=NC(C)=C(C)N2C=C(C(=O)OCC)C=C1OCC1=CC=CC=C1 XFZLCTUONFKKGV-UHFFFAOYSA-N 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
210000004211 gastric acid Anatomy 0.000 description 3
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 3
238000000746 purification Methods 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000000126 substance Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
AGGKIUHIZDLLQA-UHFFFAOYSA-N (2,3-dimethyl-8-phenylmethoxyimidazo[1,2-a]pyridin-6-yl)methanol Chemical compound C=1C(CO)=CN2C(C)=C(C)N=C2C=1OCC1=CC=CC=C1 AGGKIUHIZDLLQA-UHFFFAOYSA-N 0.000 description 2
RCWWVMBAINFWOV-SZVBFZGTSA-N (7r,8r,9r)-2,3,7-trimethyl-9-phenyl-9,10-dihydro-8h-imidazo[1,2-h][1,7]naphthyridine-7,8-diol Chemical compound C1([C@H]2NC=3C4=NC(=C(N4C=CC=3[C@@](C)(O)[C@@H]2O)C)C)=CC=CC=C1 RCWWVMBAINFWOV-SZVBFZGTSA-N 0.000 description 2
HZARBZKYLFMYGP-RHSMWYFYSA-N (8r,9r)-8-hydroxy-2,3-dimethyl-9-phenyl-9,10-dihydro-8h-imidazo[1,2-h][1,7]naphthyridin-7-one Chemical compound C1([C@H]2NC=3C4=NC(=C(N4C=CC=3C(=O)[C@@H]2O)C)C)=CC=CC=C1 HZARBZKYLFMYGP-RHSMWYFYSA-N 0.000 description 2
REFFAOXFNWGTCG-RDGATRHJSA-N (8s,9r)-8-benzyl-8-hydroxy-2,3-dimethyl-9-phenyl-9,10-dihydroimidazo[1,2-h][1,7]naphthyridin-7-one Chemical compound C1([C@H]2NC=3C4=NC(=C(N4C=CC=3C(=O)[C@@]2(CC=2C=CC=CC=2)O)C)C)=CC=CC=C1 REFFAOXFNWGTCG-RDGATRHJSA-N 0.000 description 2
125000004814 1,1-dimethylethylene group Chemical group [H]C([H])([H])C([*:1])(C([H])([H])[H])C([H])([H])[*:2] 0.000 description 2
125000004815 1,2-dimethylethylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([*:2])C([H])([H])[H] 0.000 description 2
125000004816 2,2-dimethylethylene group Chemical group [H]C([H])([H])C([*:2])(C([H])([H])[H])C([H])([H])[*:1] 0.000 description 2
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
YTVAVHFVWDJYTF-UHFFFAOYSA-N 6,8-dibromo-2,3-dimethylimidazo[1,2-a]pyridine Chemical compound BrC1=CC(Br)=CN2C(C)=C(C)N=C21 YTVAVHFVWDJYTF-UHFFFAOYSA-N 0.000 description 2
CVQJKRFLJGJENU-UHFFFAOYSA-N 6-bromo-2,3-dimethyl-8-phenylmethoxyimidazo[1,2-a]pyridine Chemical compound C=1C(Br)=CN2C(C)=C(C)N=C2C=1OCC1=CC=CC=C1 CVQJKRFLJGJENU-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 2
241000590002 Helicobacter pylori Species 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
108010079943 Pentagastrin Proteins 0.000 description 2
208000008469 Peptic Ulcer Diseases 0.000 description 2
PQGAHNJECSVDEI-UHFFFAOYSA-N [CH2]CCCCC Chemical compound [CH2]CCCCC PQGAHNJECSVDEI-UHFFFAOYSA-N 0.000 description 2
230000010933 acylation Effects 0.000 description 2
RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
UHURJXXAXXMMLW-UHFFFAOYSA-N but-3-en-1-yl radical Chemical compound [CH2]CC=C UHURJXXAXXMMLW-UHFFFAOYSA-N 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
239000000812 cholinergic antagonist Substances 0.000 description 2
MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
229960002626 clarithromycin Drugs 0.000 description 2
AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 2
229940126214 compound 3 Drugs 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
230000001351 cycling effect Effects 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
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239000011777 magnesium Substances 0.000 description 1
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229910052751 metal Inorganic materials 0.000 description 1
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YRGDZDTZQNSUMT-UHFFFAOYSA-N methanesulfonic acid phenylmethanesulfonic acid Chemical compound CS(O)(=O)=O.OS(=O)(=O)Cc1ccccc1 YRGDZDTZQNSUMT-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
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230000003000 nontoxic effect Effects 0.000 description 1
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YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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150000002960 penicillins Chemical class 0.000 description 1
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208000000689 peptic esophagitis Diseases 0.000 description 1
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230000000144 pharmacologic effect Effects 0.000 description 1
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
229960000620 ranitidine Drugs 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
BZGIPVGCJGXQTA-UHFFFAOYSA-N s-[2-(diethylamino)ethyl] n,n-diphenylcarbamothioate Chemical compound C=1C=CC=CC=1N(C(=O)SCCN(CC)CC)C1=CC=CC=C1 BZGIPVGCJGXQTA-UHFFFAOYSA-N 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
OLRJXMHANKMLTD-UHFFFAOYSA-N silyl Chemical compound [SiH3] OLRJXMHANKMLTD-UHFFFAOYSA-N 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
208000018556 stomach disease Diseases 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229950004351 telenzepine Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
229960002372 tetracaine Drugs 0.000 description 1
GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
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238000004448 titration Methods 0.000 description 1
239000003440 toxic substance Substances 0.000 description 1
239000003204 tranquilizing agent Substances 0.000 description 1
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229920002554 vinyl polymer Polymers 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
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235000013343 vitamin Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

ES01917121T 2000-03-29 2001-03-28 Derivados de imidazopiridinas alquiladas. Expired - Lifetime ES2267737T3 (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP00106696		2000-03-29
EP00106696		2000-03-29

Publications (1)

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ES2267737T3 true ES2267737T3 (es)	2007-03-16

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Country Status (23)

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US (1)	US6916825B2 (de)
EP (1)	EP1313739B1 (de)
JP (1)	JP2003528876A (de)
KR (1)	KR100823762B1 (de)
CN (1)	CN1213049C (de)
AT (1)	ATE332302T1 (de)
AU (1)	AU783764B2 (de)
BR (1)	BR0109542A (de)
CA (1)	CA2404460A1 (de)
CZ (1)	CZ20023116A3 (de)
DE (1)	DE60121345T2 (de)
EA (1)	EA005215B1 (de)
ES (1)	ES2267737T3 (de)
HR (1)	HRP20020853A2 (de)
HU (1)	HUP0300578A3 (de)
IL (1)	IL151201A0 (de)
MX (1)	MXPA02009552A (de)
NO (1)	NO20024597D0 (de)
NZ (1)	NZ520835A (de)
PL (1)	PL357811A1 (de)
SK (1)	SK13872002A3 (de)
WO (1)	WO2001072754A1 (de)
ZA (1)	ZA200207636B (de)

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JP2003528878A (ja)	2000-03-29	2003-09-30	アルタナファルマアクチエンゲゼルシャフト	イミダゾピリジン誘導体のプロドラッグ
KR20020082494A (ko) *	2000-03-29	2002-10-31	알타나 파마 아게	위장 질환 치료용피라노[2,3-씨]이미다조[1,2-에이]피리딘 유도체
AU2002210563B2 (en)	2000-10-25	2007-03-01	Altana Pharma Ag	Polysubstituted imidazopyridines as gastric secretion inhibitors
CN1656096A (zh) *	2001-08-03	2005-08-17	奥坦纳医药公司	用于治疗胃肠病症的烷基－取代的咪唑吡啶
DE10145457A1 (de) *	2001-09-14	2003-04-03	Basf Ag	Substituierte Imidazo[1,2-a]-5,6,7,8-tetrahydropyridin-8-one, Verfahren zu ihrer Herstellung, sowie deren Verwendung zur Herstellung von Imidazo[1,2,-a]pyridinen
HRP20040834A2 (en)	2002-02-15	2005-06-30	Altana Pharma Ag	Tricyclic n-acyl compounds
HRP20050528A2 (en)	2002-11-19	2006-06-30	Altana Pharma Ag	8-substituted imidazopyridines
PL375933A1 (en) *	2002-12-20	2005-12-12	Altana Pharma Ag	8-trialkylsiloxy-2-methyl-9-phenyl-7-oxo-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridines
BRPI0407541A (pt) *	2003-02-17	2006-02-14	Altana Pharma Ag	combinações e uso de compostos farmaceuticamente ativos selecionados
AR044129A1 (es)	2003-05-06	2005-08-24	Altana Pharma Ag	Compuestos intermedios de imidazopiridina. proceso de preparacion.
EP1682133A1 (de)	2003-11-03	2006-07-26	AstraZeneca AB	Imidazo-1,2-a-pyridin-derivate zur behandlung von beschwerdefreiem gastroösophagealem reflux
WO2005058894A1 (en)	2003-12-19	2005-06-30	Altana Pharma Ag	Intermediates for the preparation of tricyclic dihydropyrano -imidazo -pyridines derivatives
US7215655B2 (en) *	2004-01-09	2007-05-08	Interdigital Technology Corporation	Transport format combination selection in a wireless transmit/receive unit
AR047605A1 (es) *	2004-02-17	2006-01-25	Altana Pharma Ag	Imidazopiridinas triciclicas e intermediarios en la sintesis de las mismas,sus procesos de preparacion,composiciones farmaceuticas que los contienen y usos.
AU2005291284A1 (en) *	2004-10-01	2006-04-13	Altana Pharma Ag	Substituted tricyclic benzimidazoles
EP1934215A1 (de) *	2005-09-22	2008-06-25	Nycomed GmbH	Isotopensubstituierte imidazopyridinderivate zur behandlung von erkrankungen des magen-darm-trakts
WO2008058990A1 (en) *	2006-11-16	2008-05-22	Nycomed Gmbh	7,7-disubstituted pyrano-[2,3-c]-imidazo-[1,2-a]-pyridine derivatives and their use as gastric acid secretion inhibitors
JP5757864B2 (ja) *	2008-05-20	2015-08-05	ニューロジェシックス，インコーポレイテッド	水溶性アセトアミノフェン類似体
AU2009249069A1 (en)	2008-05-20	2009-11-26	Neurogesx, Inc.	Carbonate prodrugs and methods of using the same
WO2016090382A1 (en) *	2014-12-06	2016-06-09	Intra-Cellular Therapies, Inc.	Organic compounds

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Publication number	Priority date	Publication date	Assignee	Title
US4468400A (en) *	1982-12-20	1984-08-28	Schering Corporation	Antiulcer tricyclic imidazo [1,2-a]pyridines
SE9401197D0 (sv) *	1994-04-11	1994-04-11	Astra Ab	Active compounds
BR9807883A (pt) *	1997-03-24	2000-02-22	Byk Gulden Lomberg Chem Fab	Compostos de tetraidropirido
CA2289542A1 (en) *	1997-05-28	1998-12-03	Byk Gulden Lomberg Chemische Fabrik Gmbh	Fused dihydropyrans
HUP0001555A3 (en)	1997-10-30	2001-01-29	Altana Pharma Ag	Tetrahydro-imidazo-naphthyridine derivatives, pharmaceutical compositions thereof and process for their preparation
WO2001072757A1 (en) *	2000-03-29	2001-10-04	Altana Pharma Ag	Tricyclic imidazopyridines
KR20020082494A (ko) *	2000-03-29	2002-10-31	알타나 파마 아게	위장 질환 치료용피라노[2,3-씨]이미다조[1,2-에이]피리딘 유도체
JP2003528878A (ja) *	2000-03-29	2003-09-30	アルタナファルマアクチエンゲゼルシャフト	イミダゾピリジン誘導体のプロドラッグ

2001
- 2001-03-28 CZ CZ20023116A patent/CZ20023116A3/cs unknown
- 2001-03-28 MX MXPA02009552A patent/MXPA02009552A/es active IP Right Grant
- 2001-03-28 AU AU44225/01A patent/AU783764B2/en not_active Ceased
- 2001-03-28 EP EP01917121A patent/EP1313739B1/de not_active Expired - Lifetime
- 2001-03-28 ES ES01917121T patent/ES2267737T3/es not_active Expired - Lifetime
- 2001-03-28 EA EA200200876A patent/EA005215B1/ru not_active IP Right Cessation
- 2001-03-28 US US10/240,039 patent/US6916825B2/en not_active Expired - Fee Related
- 2001-03-28 DE DE60121345T patent/DE60121345T2/de not_active Expired - Fee Related
- 2001-03-28 WO PCT/EP2001/003507 patent/WO2001072754A1/en not_active Ceased
- 2001-03-28 JP JP2001570663A patent/JP2003528876A/ja not_active Withdrawn
- 2001-03-28 NZ NZ520835A patent/NZ520835A/en unknown
- 2001-03-28 IL IL15120101A patent/IL151201A0/xx unknown
- 2001-03-28 CA CA002404460A patent/CA2404460A1/en not_active Abandoned
- 2001-03-28 AT AT01917121T patent/ATE332302T1/de not_active IP Right Cessation
- 2001-03-28 HR HR20020853A patent/HRP20020853A2/hr not_active Application Discontinuation
- 2001-03-28 KR KR1020027012843A patent/KR100823762B1/ko not_active Expired - Fee Related
- 2001-03-28 PL PL01357811A patent/PL357811A1/xx not_active Application Discontinuation
- 2001-03-28 CN CNB018071619A patent/CN1213049C/zh not_active Expired - Fee Related
- 2001-03-28 BR BR0109542-0A patent/BR0109542A/pt not_active Application Discontinuation
- 2001-03-28 HU HU0300578A patent/HUP0300578A3/hu unknown
- 2001-03-28 SK SK1387-2002A patent/SK13872002A3/sk unknown
2002
- 2002-09-23 ZA ZA200207636A patent/ZA200207636B/xx unknown
- 2002-09-25 NO NO20024597A patent/NO20024597D0/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2404460A1 (en)	2001-10-04
US6916825B2 (en)	2005-07-12
KR100823762B1 (ko)	2008-04-21
ZA200207636B (en)	2003-04-04
IL151201A0 (en)	2003-04-10
WO2001072754A9 (en)	2004-05-06
JP2003528876A (ja)	2003-09-30
MXPA02009552A (es)	2004-05-14
WO2001072754A8 (en)	2003-02-13
NZ520835A (en)	2004-05-28
HK1056173A1 (en)	2004-02-06
NO20024597L (no)	2002-09-25
DE60121345D1 (de)	2006-08-17
CN1422274A (zh)	2003-06-04
HUP0300578A2 (hu)	2003-07-28
CZ20023116A3 (cs)	2003-01-15
HUP0300578A3 (en)	2009-01-28
US20030158193A1 (en)	2003-08-21
DE60121345T2 (de)	2007-07-19
EA200200876A1 (ru)	2003-04-24
CN1213049C (zh)	2005-08-03
EP1313739B1 (de)	2006-07-05
ATE332302T1 (de)	2006-07-15
NO20024597D0 (no)	2002-09-25
PL357811A1 (en)	2004-07-26
KR20030015221A (ko)	2003-02-20
HRP20020853A2 (en)	2005-02-28
AU783764B2 (en)	2005-12-01
SK13872002A3 (sk)	2003-02-04
EA005215B1 (ru)	2004-12-30
BR0109542A (pt)	2003-06-10
EP1313739A1 (de)	2003-05-28
AU4422501A (en)	2001-10-08
WO2001072754A1 (en)	2001-10-04

Publication	Publication Date	Title
ES2253376T3 (es)	2006-06-01	Profarmacos de derivados de imidazopiridina.
BG65195B1 (bg)	2007-06-29	Тетрахидропиридоетери
KR100823762B1 (ko)	2008-04-21	알킬화된 이미다조피리딘 유도체
ES2199810T3 (es)	2004-03-01	Haloalcoxi-imidazonaftiridinas.
JP2001526703A (ja)	2001-12-18	縮合ジヒドロピラン
ES2219890T3 (es)	2004-12-01	Compuestos tetrahidropirido.
ES2243788T3 (es)	2005-12-01	Imidazopiridinas triciclicas.
ES2283408T3 (es)	2007-11-01	Imidazopiridinas triciclicas.
ES2298233T3 (es)	2008-05-16	Derivados de pirano(2,3-c)imidazo(1,2-a)piridina para el tratamiento de trastornos gastrointestinales.
HK1056173B (en)	2007-01-12	Alkylated imidazopyridine derivatives